Corticosteroids (CS) are common treatments for managing diseases that cause inflammation, such as arthritis; however, they also have side-effects on sugar metabolism and on bones. Even though they are used commonly, we don’t really have a clear understanding about the association of use of these drugs with the risk of developing either diabetes (DM) or osteoporosis.
This study will determine if oral or injected corticosteroid use in adults is a risk factor for: 1) developing diabetes; or 2) intensification of diabetes treatment; or 3) developing osteoporosis. The study will compare people who use steroids with similar patients.
The number of people who are first diagnosed with diabetes and/or osteoporosis will be compared between those who take the drug and those who do not. The study will provide estimates of the difference (if any) of the risks associated with being treated with corticosteroids and the likelihood of diabetes and of osteoporosis.
Systemic corticosteroids (CS) are important for managing inflammation, but have profound endocrine effects on glucose metabolism and bone turnover. Few consistent data exist describing the association of CS and risks of developing either diabetes mellitus (DM) or osteoporosis, and progression of DM.
The study will determine if oral or intravenous CS (OIVCS) exposure in adults is a risk factor for: 1) developing DM (co-primary objective); 2) intensification of DM treatment (co-primary); 3) developing osteoporosis (secondary); and 4) changes in vascular disease risk factors in Type 2 DM (exploratory); testing the hypothesis that disturbance in glucose metabolism is driven by OIVCS in a dose-dependent manner with both acute and chronic cumulative effects.
A matched cohort design comparing OIVCS-exposed versus non-exposed patients is proposed drawn from CPRD GOLD (upto December 2019) with linked hospital data. The studies of incident diabetes and osteoporosis follow-up patients from first-ever OIVCS prescription whereas for intensification of DM treatment, from first OIVCS prescription after DM diagnosis. OIVCS-exposed patients will be matched to non-OIVCS patients similar in baseline characteristics from the same GP practice.
OIVCS exposure will be measured by intended time exposed for ‘on’ episodes, dose intensity, and cumulative exposure. Concomitant prescribed CS either inhaled, topically applied, or otherwise administered will also be assessed.
The primary analyses will be time-to-event, namely first diagnosis of DM, first intensification of DM glycaemia management, or first diagnosis of either osteoporosis or fragility fracture, respectively using Cox regression modelling with mixed effects, the principal output will be the hazard ratios (and their 95% confidence intervals) for the exposures and covariates on the outcomes of interest.
The study will provide population-wide estimates of the excess metabolic risks associated with CS prescribing adding to the current body of knowledge which hitherto has comprised smaller studies of specific clinical subgroups with limited generalisability.
Incident diabetes mellitus (DM); DM therapy intensification; incident osteoporosis (including fragility fracture); change in glycosylated haemoglobin; change in random blood glucose; body mass index (BMI) change; blood pressure change; lipid profile change;
Samuel Adamsson Eryd - Chief Investigator - AstraZeneca AB (Sweden)
Ellen Hubbuck - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Craig Currie - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Hungta Chen - Collaborator - Astra Zeneca Inc - USA
Karolina Andersson Sundell - Collaborator - Astra Zeneca R&D Molndal Sweden
Philip Ambery - Collaborator - AstraZeneca Ltd - UK Headquarters
Phillip Hunt - Collaborator - Astra Zeneca Inc - USA
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Craig Currie - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
HES Admitted Patient Care